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Original article| Volume 102, ISSUE 4, P509-521, October 1983

Effects of amphotericin B and cholera toxin on intestinal transport in the rat

An in vivo model for the effects of dihydroxy bile acids and fatty acids on intestinal transport
  • H.V. Ammon
    Correspondence
    Reprint requests: Helmut V. Ammon, M.D., Gastroenterology Section/111C, Veterans Administration Center, Milwaukee, Wisc. 53193.
    Affiliations
    From the Gastroenterology Section, Medical Service, Veterans Administration Center, Milwaukee, Wisc., USA

    From the Department of Medicine, the Medical College of Wisconsin, Milwaukee, Wisc., USA
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  • L.G. Walter
    Affiliations
    From the Gastroenterology Section, Medical Service, Veterans Administration Center, Milwaukee, Wisc., USA

    From the Department of Medicine, the Medical College of Wisconsin, Milwaukee, Wisc., USA
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  • R.F. Loeffler
    Affiliations
    From the Gastroenterology Section, Medical Service, Veterans Administration Center, Milwaukee, Wisc., USA

    From the Department of Medicine, the Medical College of Wisconsin, Milwaukee, Wisc., USA
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      Abstract

      In vivo perfusion experiments were performed in the rat jejunum and colon to test the hypothesis that the changes in intestinal solute transport induced by dihydroxy bile acids and fatty acids are the result of the combined effects of fluid secretion and enhancement of mucosal permeability. The hypothesis predicts that absorption of organic solutes will be reduced in inverse relationship to the absorption rates under control conditions and that absorption of small, nonabsorbable solutes such as mannitol will be enhanced by these agents. Fluid secretion was induced either by administering cholera toxin or by increasing the osmolality of the perfusion solution to 365 mOsm/L. Permeability was enhanced by adding amphotericin B, 50 μg/ml, to the perfusion solutions. The isotonic perfusion solutions contained 11.2 mM glucose and 4 mM triethylene, tetraethylene, pentaethylene, and hexaethylene glycol or mannitol as probes of passive permeability. In the jejunum cholera toxin induced fluid and electrolyte secretion and reduced organic solute absorption to a small but significant degree (p < 0.05). Amphotericin B alone enhanced absorption of organic solutes, water, and electrolytes (p < 0.01). In the presence of fluid secretion induced by an osmotic load, only absorption of triethylene and pentaethylene glycol was reduced. Addition of amphotericin B after exposure to cholera toxin or to the hypertonic solutions resulted in a further significant reduction of absorption of glucose and ethylene glycols (p < 0.05). The combination of amphotericin B and cholera toxin resulted in enhanced absorption of mannitol (p < 0.02). Similarly, 5 mM deoxycholate enhanced jejunal absorption of mannitol (p < 0.01) and reduced the absorption of glucose and the low-molecular-weight ethylene glycols (p < 0.01). In the colon the administration of amphotericin B after the exposure to cholera toxin resulted in enhanced absorption of glucose (p < 0.05) in spite of continuing fluid secretion. The combination of fluid secretion and enhancement of mucosal permeability, therefore, reproduced all in vivo effects of bile acids and fatty acids on intestinal transport of organic solutes.

      Abbreviations:

      polyethylene glycol 4000 ((PEG)), inner diameter ((ID))
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